title: Mitoxantrone does not restore the impaired suppressive function of natural regulatory T cells in patients suffering from multiple sclerosis. A longitudinal ex vivo and in vitro study.
abstract: CD4+CD25+ regulatory T (T(reg)) cells play a major role in controlling autoimmunity by suppressing self-reactive T cells. Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system, where T cells are of major importance. T(reg) cell frequency and function are potential therapeutic targets of MS treatment. Mitoxantrone (MX) is a potent immunosuppressant for the treatment of active MS. We investigated the long-term effects of MX on the suppressive function of T(reg) after mitogen and myelin basic protein (MBP) stimulation in 20 MX-treated patients. MX therapy did not restore the reduced suppressive activity of a mixture of CD25(intermediate) or CD25(high) expressing T(reg) (healthy controls, MBP: 37.3%; MS patients, MBP: -1.9 vs. 6.6% suppression after MX treatment for 6 months, p > 0.2). The frequency of T(reg) cells was not affected by MX. A single infusion of MX (10 mg/m(2) body surface) induced a selective and persistent reduction of approximately 30% of absolute and relative counts of B lymphocytes (p < 0.05). MX therapy does not influence T(reg) cell frequency or function. MX seems to exhibit its efficacy in MS mainly by a suppression of humoral immunity.
authors.affiliation: Department of Neurology, University Clinic Essen, University of Duisburg-Essen, Essen, Germany. norman.putzki@uni-due.de
authors.forename: Norman
authors.initials: N
authors.lastname: Putzki
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.forename: Ernst
authors.initials: E
authors.lastname: Kreuzfelder
authors.forename: Hans
authors.initials: H
authors.lastname: Grosse-Wilde
authors.forename: H C
authors.initials: HC
authors.lastname: Diener
authors.forename: Volker
authors.initials: V
authors.lastname: Limmroth
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008942:Mitoxantrone / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D008942:Mitoxantrone